Large-scale disaster situations put considerable demands on existing medical infrastructure, as well as local governing and safety agencies. When the additional factor of ionizing radiation and exposure of humans is part of the emergency, the lack of effective assessment tools and management strategies can easily become overwhelming. As part of efforts to devise methods and technologies that will address this critical need, this proposal is designed to develop and evaluate two radiation- sensitive endpoints that can be obtained from a small volume blood sample. The goal is to create an analytical platform that could be integrated into mobile response units that can quickly survey the thousands of subjects expected in certain emergency triage situations. The key to delivering useful dose/exposure estimation with a sufficiently rapid turnaround is the combination of cell enrichment via immunomagnetic technologies with high throughput analytical platforms that employ multi-well plates, e.g. 384 or 1536 well. An ultra-high throughput method that enumerates circulating lymphocytes will serve as an initial screen that can rapidly survey and flag subjects for further analysis. Using the same blood sample, the confirmatory assay will employ flow cytometric assessment of micronucleated reticulocytes as a marker of radiation-induced chromosome damage. This two-stage approach will enable the first screen to quickly dismiss the majority of individuals that have received minimal-to-no exposure and the subsequent assay will focus on definitive identification of subjects that will require further medical care. By quickly and efficiently sending the worried-well home, more effective allocation of resources and care can be directed where it is ultimately needed. Such an approach is critical to ensuring an immediate and sufficient response to large-scale emergencies such as those presented by exposure of human populations to ionizing radiation. PUBLIC HEALTH RELEVANCE: Accidental or intentional exposure of human populations to ionizing radiation will not only directly impact public health, but will also affect economics, politics and societies worldwide. The development of tools and strategies to assess and mitigate these impacts are of critical national and global importance. This proposal seeks to generate a rapid high throughput approach using two established biomarkers of radiation damage to determine exposure of individual humans in point-of-care triage settings.